In a groundbreaking study, researchers at Mayo Clinic have discovered that a sugar molecule used by cancer cells to evade the immune system could also help treat type 1 diabetes. The team, led by immunology researcher Virginia Shapiro, Ph.D., found that dressing up beta cells with the same sugar molecule, known as sialic acid, enabled the immune system to tolerate them.

Type 1 diabetes is a chronic autoimmune condition in which the immune system mistakenly attacks pancreatic beta cells that produce insulin. This leads to an estimated 1.3 million people in the U.S. suffering from the disease. In their studies, Shapiro’s team used a cancer mechanism and turned it on its head by applying it to type 1 diabetes.

The researchers took a closer look at a preclinical model of type 1 diabetes and found that beta cells engineered to produce an enzyme called ST8Sia6, which increases sialic acid on the surface of tumor cells, were not attacked by the immune system. In fact, they were 90% effective in preventing the development of type 1 diabetes.

The team’s findings show that it is possible to engineer beta cells that do not prompt an immune response. This breakthrough has the potential to improve therapy for patients with type 1 diabetes, who currently rely on synthetic insulin or transplantation of pancreatic islet cells with immunosuppression.

Dr. Shapiro aims to explore using the engineered beta cells in transplantable islet cells without the need for immunosuppression. While still in the early stages, this study may be one step toward improving care for patients with type 1 diabetes.

The silent threat of hearing loss and loneliness is fueling memory decline, particularly among older adults. Researchers at the University of Geneva have analyzed data from 33,000 people across Europe and identified three distinct profiles related to social isolation and perceived loneliness. The findings show that hearing loss accelerates cognitive decline, especially among individuals who feel lonely, regardless of whether they are socially isolated.

The World Health Organization (WHO) predicts that nearly 2.5 billion people will experience hearing loss or impairment by 2050. More than 25% of people over the age of 60 experience disabling hearing impairment, which is linked to a significantly increased risk of cognitive decline in later life. This risk may be two to three times higher for those affected.

The study used data from the SHARE survey (Survey of Health, Ageing and Retirement in Europe), which examines the health and aging of Europeans aged 50 and over. The researchers identified three distinct profiles related to social isolation and perceived loneliness:

1. Isolation: This profile refers to individuals who are socially isolated, meaning they have few or no social connections.
2. Loneliness: This profile refers to individuals who feel lonely, but may not be socially isolated. They may have social connections, but still feel disconnected from others.
3. Deafness and isolation: This profile refers to individuals who experience both hearing loss and social isolation.

The study found that people in the “deafness and isolation” profile had the most accelerated cognitive decline, while those in the “loneliness” profile also experienced significant declines. However, it’s essential to note that the “loneliness” profile was not necessarily linked to social isolation, but rather a subjective feeling of being disconnected from others.

The researchers emphasize the importance of addressing both hearing loss and the social and emotional dimensions of individuals in efforts to prevent cognitive decline. This is particularly crucial for people who are not socially isolated but still feel lonely, as simple hearing interventions may be enough to help them engage more fully in social life and protect their cognitive health.

In conclusion, the silent threat of hearing loss and loneliness is fueling memory decline, especially among older adults. It’s essential to address both aspects to prevent cognitive decline and ensure a healthy and happy aging process.

The way we perceive and respond to physical pain is more than just a physical sensation – it also carries an emotional weight. This emotional discomfort can motivate us to take action and helps us learn to associate negative feelings with situations so we can avoid them in the future. However, when our ability to tolerate pain becomes too sensitive or lasts too long, it can result in chronic and affective pain disorders such as fibromyalgia, migraines, and post-traumatic stress disorder (PTSD).

Researchers at the Salk Institute have now identified a brain circuit that gives physical pain its emotional tone. Published in the Proceedings of the National Academy of Sciences, the study reveals a group of neurons in the central brain area called the thalamus that appears to mediate the emotional or affective side of pain in mice.

The prevailing view for decades was that the brain processes sensory and emotional aspects of pain through separate pathways. However, this new pathway challenges the textbook understanding of how pain is processed in the brain and body. The physical sensation of pain allows you to immediately detect it, assess its intensity, and identify its source, while the affective part of pain makes it unpleasant.

This distinction is crucial because most people start to perceive pain at the same stimulus intensities. However, our ability to tolerate pain varies greatly, with some individuals being more sensitive than others. The affective processing determines how much we suffer or feel threatened by pain. If this becomes too sensitive or lasts too long, it can result in a pain disorder.

The researchers used advanced techniques to manipulate the activity of specific brain cells and discovered a new spinothalamic pathway in mice. In this circuit, pain signals are sent from the spinal cord into a different part of the thalamus, which has connections to the amygdala, the brain’s emotional processing center. This particular group of neurons can be identified by their expression of CGRP (calcitonin gene-related peptide).

When these CGRP neurons were “turned off,” the mice still reacted to mild pain stimuli but didn’t seem to associate lasting negative feelings with these situations. However, when these same neurons were “turned on,” the mice showed clear signs of distress and learned to avoid that area, even when no pain stimuli had been used.

“Pain processing is not just about nerves detecting pain; it’s about the brain deciding how much that pain matters,” says first author Sukjae Kang. Understanding the biology behind these two distinct processes will help us find treatments for the kinds of pain that don’t respond to traditional drugs.

Many chronic pain conditions, such as fibromyalgia and migraine, involve long, intense, unpleasant experiences of pain often without a clear physical source or injury. Some patients also report extreme sensitivity to ordinary stimuli like light, sound, or touch which others would not perceive as painful.

Han says overactivation of the CGRP spinothalamic pathway may contribute to these conditions by making the brain misinterpret or overreact to sensory inputs. In fact, transcriptomic analysis of the CGRP neurons showed that they express many of the genes associated with migraine and other pain disorders.

Several CGRP blockers are already being used to treat migraines. This study may help explain why these medications work and could inspire new nonaddictive treatments for affective pain disorders. Han also sees potential relevance for psychiatric conditions that involve heightened threat perception, such as PTSD. Quieting this pathway with CGRP blockers could offer a new approach to easing fear, avoidance, and hypervigilance in trauma-related disorders.

Importantly, the relationship between the CGRP pathway and the psychological pain associated with social experiences like grief, loneliness, and heartbreak remains unclear and requires further study.

“Our discovery of the CGRP affective pain pathway gives us a molecular and circuit-level explanation for the difference between detecting physical pain and suffering from it,” says Han. “We’re excited to continue exploring this pathway and enabling future therapies that can reduce this suffering.”